Selection of Schizochytrium limacinum mutants based on butanol tolerance

Background: Mutation breeding is one of the most important routes to achieving high docosahexaenoic acid (DHA) productivity using Schizochytrium. However, few selection strategies have been reported that aim to generate a high DHA content in Schizochytrium lipids. Results: First, culture temperature altered the butanol tolerance of Schizochytrium limacinum B4D1. Second, S. limacinum E8 was obtained by selecting mutants with high butanol tolerance. This mutant exhibited a 17.97% lower proportion of DHA than the parent strain S. limacinum B4D1. Third, a negative selection strategy was designed in which S. limacinum F6, a mutant with poor butanol tolerance, was obtained. The proportion of DHA in S. limacinum F6 was 11.22% higher than that of parent strain S. limacinum B4D1. Finally, the performances of S. limacinum B4D1, E8 and F6 were compared. These three strains had different fatty acid profiles, but there was no statistical difference in their biomasses and lipid yields. Conclusion: It was feasible to identified the relative DHA content of S. limacinum mutants based on their butanol tolerance

Design strategies of tumor-targeted delivery systems based on 2D nanomaterials

Conventional chemotherapy and radiotherapy are nonselective and nonspecific for cell killing, causing serious side effects and threatening the lives of patients. It is of great significance to develop more accurate tumor-targeting therapeutic strategies. Nanotechnology is in a leading position to provide new treatment options for cancer, and it has great potential for selective targeted therapy and controlled drug release. 2D nanomaterials (2D NMs) have broad application prospects in the field of tumor-targeted delivery systems due to their special structure-based functions and excellent optical, electrical, and thermal properties. This review emphasizes the design strategies of tumor-targeted delivery systems based on 2D NMs from three aspects: passive targeting, active targeting, and tumor-microenvironment targeting, in order to promote the rational application of 2D NMs in clinical practice.This work was supported by the Guangdong Basic and Applied Basic Research Foundation (Nos. 2021A1515110657 and 2022A1515010056), Shenzhen Science and Technology Program (Grant No. RCBS20210609104513023), National Natural Science Foundation of China (No. 81922037), and Shanghai Biomedical Science and Technology Support Project (No. 19441903600)

Prevalence of malnutrition and associated factors among children aged 6–24 months under poverty alleviation policy in Shanxi province, China: A cross-sectional study

Introduction: Child malnutrition continues to be a major public health issue, accounting for 54% of all child mortality globally. This study aimed to determine the prevalence of childhood malnutrition and its associated risk factors as well as to explore the best developmental strategy among infants and young children (IYC). Methodology: This cross-sectional study was conducted six months after the distribution of nutritious YingYangBao (YYB). It involved children aged 6–24 months in Shaanxi Province, China. Data were collected via interviews with parents of IYC, followed by measurements of the children’s height and weight. Data were analyzed using EpiInfo software and SPSSv.26, which encompassed descriptive statistics, Pearson Chi-square, and multivariate logistic regression analysis. Ethics approval and parents’ informed consent were attained prior to the study. Result: A total of 3431 data were analyzed in the study. The prevalence of stunting was highest among IYC between 12 and 18 months (3.9%). Prevalence of underweight (0.5%) and wasting (1.5%) were highest among IYC aged 18–24 months while the prevalence of overweight was highest among IYC aged 6–12months (9.0%). Significant associating risk factors of malnutrition were IYC from Northern Shaanxi (aOR = 2.24; 95% CI:1.68–2.98) and mothers with parity ≥3 (aOR = 1.52; 95%CI:1.10–2.10). IYC with a higher educated father (aOR = 0.79; 95%CI:0.66–0.95), YYB intervention (aOR = 0.77; 95%CI:0.65–0.90), correct supplementary food time (aOR = 0.84; 95%CI:0.71–1.00) and separate supplementary food preparation (aOR = 0.79; 95% CI:0.66–0.95) were significantly associated with lower risk of malnutrition. Conclusion: Even though the prevalence of stunting, underweight, and wasting were relatively low (<5%), there is still a need to strengthen existing policies on child nutrition

Solute Carrier Family 1 (SLC1A1) Contributes to Susceptibility and Psychopathology Symptoms of Schizophrenia in the Han Chinese Population

Objective: Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamate hypothesis describes one possible pathogenesis of SZ. The solute carrier family 1 gene (SLC1A1) is one of several genes thought to play a critical role in regulating the glutamatergic system and is strongly implicated in the pathophysiology of SZ. In this study, we identify polymorphisms of the SLC1A1 gene that may confer susceptibility to SZ in the Han Chinese population. Methods: We genotyped 36 single-nucleotide polymorphisms (SNPs) using Illumina GoldenGate assays on a BeadStation 500G Genotyping System in 528 paranoid SZ patients and 528 healthy controls. Psychopathology was rated by the Positive and Negative Symptom Scale. Results: Significant associations were found in genotype and allele frequencies for SNPs rs10815017 (p = 0.002, 0.030, respectively) and rs2026828 (p = 0.020, 0.005, respectively) between SZ and healthy controls. There were significant associations in genotype frequency at rs6476875 (p = 0.020) and rs7024664 (p = 0.021) and allele frequency at rs3780412 (p = 0.026) and rs10974573 (p = 0.047) between SZ and healthy controls. Meanwhile, significant differences were found in genotype frequency at rs10815017 (p = 0.015), rs2026828 (p = 0.011), and rs3780411 (p = 0.040) in males, and rs7021569 in females (p = 0.020) between cases and controls when subdivided by gender. Also, significant differences were found in allele frequency at rs2026828 (p = 0.003), and rs7021569 (p = 0.045) in males, and rs10974619 in females (p = 0.044). However, those associations disappeared after Bonferroni\u27s correction (p\u27s \u3e 0.05). Significant associations were found in the frequencies of four haplotypes (AA, CA, AGA, and GG) between SZ and healthy controls (chi (2) = 3.974, 7.433, 4.699, 4.526, p = 0.046, 0.006, 0.030, 0.033, respectively). There were significant associations between rs7032326 genotypes and PANSS total, positive symptoms, negative symptoms, and general psychopathology in SZ (p = 0.002, 0.011, 0.028, 0.008, respectively). Conclusion: The present study provides further evidence that SLC1A1 may be not a susceptibility gene for SZ. However, the genetic variations of SLC1A1 may affect psychopathology symptoms

Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine based on 3D Tumour Models

Evodiamine (EVO) and rutaecarpine (RUT) are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids, and compared the results with those obtained from 2D monolayers. The drugs’ IC50 values were significantly increased from the range of 6.4–44.1 μM in 2D monolayers to 21.8–138.0 μM in 3D multicellular spheroids, which may be due to enhanced mass barrier and reduced drug penetration in 3D models. The fluorescence of EVO and RUT was measured via fluorescence spectroscopy and the cellular uptake of both drugs was characterized in 2D tumor models. The results showed that the cellular uptake concentrations of RUT increased with increasing drug concentrations. However, the EVO concentrations uptaken by the cells showed only a small change with increasing drug concentrations, which may be due to the different solubility of EVO and Rut in solvents. Overall, this study provided a new vision of the anti-tumor activity of EVO and RUT via 3D multicellular spheroids and cellular uptake through the fluorescence of compounds.Peer reviewe

Implanting MnO2 into Hexagonal Boron Nitride as Nanoadditives for Enhancing Tribological Performance

Hexagonal boron nitride nanosheets (h-BNNs) show great potential in the field of tribology due to their typical two-dimensional layered structure and are essential for replacing conventional sulfur/phosphate-containing additives. However, the large particle size and poor dispersion of h-BNs seriously restrict their green lubrication application. In this paper, MnO2@h-BNNs nanocomposites were successfully prepared by ultrasonically exfoliating a hydrothermal method. The tribological properties of MnO2@h-BNNs nanocomposites as lubricant additives in poly-alpha-olefin oil (PAO) were investigated. The results show the oil dispersed with 0.25 wt% MnO2@h-BNNs had the best friction reduction and antiwear effect with 42% and 11.2% reduction, respectively, compared with the plain oil. Through further wear surface analyzing, we verified the antiwear mechanism of additives in filling the micropits and grooves on the wear surface and forming a friction protection film including Fe2O3, MnO2, and BN on the wear surface, avoiding direct contact between the friction subsets. This can provide ideas for other lubricating oil additives

The molecular dynamic simulation on impact and friction characters of nanofluids with many nanoparticles system

Impact and friction model of nanofluid for molecular dynamics simulation was built which consists of two Cu plates and Cu-Ar nanofluid. The Cu-Ar nanofluid model consisted of eight spherical copper nanoparticles with each particle diameter of 4 nm and argon atoms as base liquid. The Lennard-Jones potential function was adopted to deal with the interactions between atoms. Thus motion states and interaction of nanoparticles at different time through impact and friction process could be obtained and friction mechanism of nanofluids could be analyzed. In the friction process, nanoparticles showed motions of rotation and translation, but effected by the interactions of nanoparticles, the rotation of nanoparticles was trapped during the compression process. In this process, agglomeration of nanoparticles was very apparent, with the pressure increasing, the phenomenon became more prominent. The reunited nanoparticles would provide supporting efforts for the whole channel, and in the meantime reduced the contact between two friction surfaces, therefore, strengthened lubrication and decreased friction. In the condition of overlarge positive pressure, the nanoparticles would be crashed and formed particles on atomic level and strayed in base liquid

Functional redundancy between DNA ligases I and III in DNA replication in vertebrate cells

In eukaryotes, the three families of ATP-dependent DNA ligases are associated with specific functions in DNA metabolism. DNA ligase I (LigI) catalyzes Okazaki-fragment ligation at the replication fork and nucleotide excision repair (NER). DNA ligase IV (LigIV) mediates repair of DNA double strand breaks (DSB) via the canonical non-homologous end-joining (NHEJ) pathway. The evolutionary younger DNA ligase III (LigIII) is restricted to higher eukaryotes and has been associated with base excision (BER) and single strand break repair (SSBR). Here, using conditional knockout strategies for LIG3 and concomitant inactivation of the LIG1 and LIG4 genes, we show that in DT40 cells LigIII efficiently supports semi-conservative DNA replication. Our observations demonstrate a high functional versatility for the evolutionary new LigIII in DNA replication and mitochondrial metabolism, and suggest the presence of an alternative pathway for Okazaki fragment ligation

PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways

Poly(ADP-ribose)polymerase 1 (PARP-1) recognizes DNA strand interruptions in vivo and triggers its own modification as well as that of other proteins by the sequential addition of ADP-ribose to form polymers. This modification causes a release of PARP-1 from DNA ends and initiates a variety of responses including DNA repair. While PARP-1 has been firmly implicated in base excision and single strand break repair, its role in the repair of DNA double strand breaks (DSBs) remains unclear. Here, we show that PARP-1, probably together with DNA ligase III, operates in an alternative pathway of non-homologous end joining (NHEJ) that functions as backup to the classical pathway of NHEJ that utilizes DNA-PKcs, Ku, DNA ligase IV, XRCC4, XLF/Cernunnos and Artemis. PARP-1 binds to DNA ends in direct competition with Ku. However, in irradiated cells the higher affinity of Ku for DSBs and an excessive number of other forms of competing DNA lesions limit its contribution to DSB repair. When essential components of the classical pathway of NHEJ are absent, PARP-1 is recruited for DSB repair, particularly in the absence of Ku and non-DSB lesions. This form of DSB repair is sensitive to PARP-1 inhibitors. The results define the function of PARP-1 in DSB repair and characterize a candidate pathway responsible for joining errors causing genomic instability and cancer